Understanding caffeine's effects in persons as they age is critical to our understanding of how caffeine affects health. This project will examine caffeine effects in 210 men and women in early (35-49 years) vs. late (50-64 years) middle age, with a secondary emphasis on variations in response as women enter menopause, a time of increased risk of heart disease and hypertension. Caffeine is widely used in significant quantities. Caffeine affects the central nervous system, cardiovascular activity, and endocrine function, and intake may increase during times of stress. Caffeine increases cardiovascular disease risk factors such as serum cholesterol and lipids. Accordingly, in a randomized crossover trial, men and women will be placed on each of two levels of caffeine intake (0 mg/day vs. 240 mg/day) for 6 days each, ending with 24-hr ambulatory monitoring of blood pressure and cortisol. Laboratory testing on day 7 will establish the effect of acute doses (200 mg x 2) on responses to mental and exercise stress. The project has 3 hypotheses: First, caffeine elevates blood pressure and cortisol secretion even with daily consumption. Second, these effects are enhanced during mental and exercise stress. Third, the effects increase from early to late middle age. It is anticipated that caffeine effects will be prominent in postmenopausal women not on estrogen replacement. Cardiovascular variables are blood pressure and hemodynamic and cardiodynamic measures taken using impedance cardiography and echocardiography. The target neuroendocrine variable will be cortisol because it is the central component of the response to stress and is responsive to caffeine. Modest elevations over long periods are thought to alter immune system function and to affect the aging process. A recent study shows that caffeine increases cortisol in the evening hours, disturbing its normal diurnal cycle. This new information should aid in evaluating caffeine's effects over the span of midlife, a time at which the cardiovascular health of women changes markedly relative to men.